Ribosomal frameshifting and dual-target antiactivation restrict quorum-sensing–activated transfer of a mobile genetic element

Integrative and conjugative elements(ICEs) facilitate horizontal transfer of multiple genetic determinants. Here we show that a programmed ribosomal frameshift(PRF) contributes to the regulation of ICE transfer. The low-frequency PRF fuses the coding sequences of two genes, resulting in a single-protein Frameshifted excision activator (FseA) that activates ICE excision. An antiactivator, QseM, known to disrupt the quorum-sensingregulator TraR, also disrupted FseA. The evolved PRF site, together with the dual-target antiactivator, QseM, likely provides robust suppression of ICE transfer in the face of the inherent biological noise of quorum-sensingautoinduction. This work illustrates how a complex multipartiteregulatory system has assembled through evolution to form a robust genetic toggle to control gene transcription and translation at both single-cell and cell-population levels.